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In 2019, The Global Initiative for Chronic Obstructive Lung Disease (GOLD) modified the grading system for patients with COPD, creating 16 subgroups (1A-4D). As part of the COPD Cohorts Collaborative International Assessment (3CIA) initiative, we aim to compare the mortality prediction of the 2015 and 2019 COPD GOLD staging systems. We studied 17 139 COPD patients from the 3CIA study, selecting those with complete data. Patients were classified by the 2015 and 2019 GOLD ABCD systems, and we compared the predictive ability for 5-year mortality of both classifications. In total, 17 139 patients with COPD were enrolled in 22 cohorts from 11 countries between 2003 and 2017; 8823 of them had complete data and were analysed. Mean±sd age was 63.9±9.8 years and 62.9% were male. GOLD 2019 classified the patients in milder degrees of COPD. For both classifications, group D had higher mortality. 5-year mortality did not differ between groups B and C in GOLD 2015; in GOLD 2019, mortality was greater for group B than C. Patients classified as group A and B had better sensitivity and positive predictive value with the GOLD 2019 classification than GOLD 2015. GOLD 2015 had better sensitivity for group C and D than GOLD 2019. The area under the curve values for 5-year mortality were only 0.67 (95% CI 0.66-0.68) for GOLD 2015 and 0.65 (95% CI 0.63-0.66) for GOLD 2019. The new GOLD 2019 classification does not predict mortality better than the previous GOLD 2015 system., Competing Interests: Conflict of interest: E. García Castillo has nothing to disclose. Conflict of interest: T. Alonso Pérez has nothing to disclose. Conflict of interest: J. Ancochea has nothing to disclose. Conflict of interest: M.T. Pastor Sanz has nothing to disclose. Conflict of interest: P. Almagro has nothing to disclose. Conflict of interest: P. Martínez-Camblor has nothing to disclose. Conflict of interest: M. Miratvilles has nothing to disclose. Conflict of interest: M. Rodríguez-Carballeira has nothing to disclose. Conflict of interest: A. Navarro has nothing to disclose. Conflict of interest: B. Lamprecht has nothing to disclose. Conflict of interest: A.S. Ramírez-García Luna has nothing to disclose. Conflict of interest: B. Kaiser has nothing to disclose. Conflict of interest: I. Alfageme has nothing to disclose. Conflict of interest: C. Casanova has nothing to disclose. Conflict of interest: C. Esteban has nothing to disclose. Conflict of interest: J.J. Soler-Cataluña has nothing to disclose. Conflict of interest: J.P. de-Torres has nothing to disclose. Conflict of interest: B.R. Celli has nothing to disclose. Conflict of interest: J.M. Marín has nothing to disclose. Conflict of interest: G. ter Riet has nothing to disclose. Conflict of interest: P. Sobradillo has nothing to disclose. Conflict of interest: P. Lange has nothing to disclose. Conflict of interest: J. García-Aymerich has nothing to disclose. Conflict of interest: J.M. Anto has nothing to disclose. Conflict of interest: A.M. Turner has nothing to disclose. Conflict of interest: M.K. Han has nothing to disclose. Conflict of interest: A. Langhammer has nothing to disclose. Conflict of interest: S.A.A. Vikjord has nothing to disclose. Conflict of interest: A. Sternberg has nothing to disclose. Conflict of interest: L. Leivseth has nothing to disclose. Conflict of interest: P. Bakke has nothing to disclose. Conflict of interest: A. Johannessen has nothing to disclose. Conflict of interest: T. Oga has nothing to disclose. Conflict of interest: B. Cosío has nothing to disclose. Conflict of interest: A. Echazarreta has nothing to disclose. Conflict of interest: N. Roche has nothing to disclose. Conflict of interest: P-R. Burgel has nothing to disclose. Conflict of interest: D.D. Sin has nothing to disclose. Conflict of interest: M.A. Puhan has nothing to disclose. Conflict of interest: J.L. López Campos has nothing to disclose. Conflict of interest: L. Carrasco has nothing to disclose. Conflict of interest: J.B. Soriano has nothing to disclose., (Copyright ©ERS 2020.)

The objective of this document was to standardise published cardiopulmonary exercise testing (CPET) protocols for improved interpretation in clinical settings and multicentre research projects. This document: 1) summarises the protocols and procedures used in published studies focusing on incremental CPET in chronic lung conditions; 2) presents standard incremental protocols for CPET on a stationary cycle ergometer and a treadmill; and 3) provides patients' perspectives on CPET obtained through an online survey supported by the European Lung Foundation. We systematically reviewed published studies obtained from EMBASE, Medline, Scopus, Web of Science and the Cochrane Library from inception to January 2017. Of 7914 identified studies, 595 studies with 26 523 subjects were included. The literature supports a test protocol with a resting phase lasting at least 3 min, a 3-min unloaded phase, and an 8- to 12-min incremental phase with work rate increased linearly at least every minute, followed by a recovery phase of at least 2-3 min. Patients responding to the survey (n=295) perceived CPET as highly beneficial for their diagnostic assessment and informed the Task Force consensus. Future research should focus on the individualised estimation of optimal work rate increments across different lung diseases, and the collection of robust normative data., Competing Interests: Conflict of interest: T. Radtke reports personal fees for registration and travel/accomodation for conferences from Vifor Pharma, outside of the submitted work. Conflict of interest: S. Crook has nothing to disclose. Conflict of interest: G. Kaltsakas has nothing to disclose. Conflict of interest: G. Louvaris has nothing to disclose. Conflict of interest: D. Berton has nothing to disclose. Conflict of interest: D.S. Urquhart has nothing to disclose. Conflict of interest: A. Kampouras has nothing to disclose. Conflict of interest: R.A. Rabinovich has nothing to disclose. Conflict of interest: S. Verges has nothing to disclose. Conflict of interest: D. Kontopidis is President of the Hellenic Cystic Fibrosis Association. Conflict of interest: J. Boyd reports is an employee of the European Lung Foundation. Conflict of interest: T. Tonia reports acting as ERS Methodologist. Conflict of interest: D. Langer has nothing to disclose. Conflict of interest: J. De Brandt has nothing to disclose. Conflict of interest: Y.M.J. Goërtz has nothing to disclose. Conflict of interest: C. Burton has nothing to disclose. Conflict of interest: M.A. Spruit reports grants and personal fees from Boehringer-Ingelheim and AstraZeneca, personal fees from GSK and Novartis, congress travel support from TEVA, and grants from the Netherlands Lung Foundation, outside the submitted work. Conflict of interest: D.C.W. Braeken has nothing to disclose. Conflict of interest: S. Dacha has nothing to disclose. Conflict of interest: F.M.E. Franssen reports personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline and TEVA, and grants and personal fees from Novartis, outside the submitted work. Conflict of interest: P. Laveneziana reports personal fees from Novartis France and Boehringer France, outside the submitted work. Conflict of interest: E. Eber has nothing to disclose. Conflict of interest: T. Troosters has nothing to disclose. Conflict of interest: J.A Neder has nothing to disclose. Conflict of interest: M.A. Puhan has nothing to disclose. Conflict of interest: R. Casaburi reports that he shares patent US 7927251 B1, relating to a linear treadmill testing protocol, issued to Los Angeles Biomedical Research Institute. Conflict of interest: I. Vogiatzis has nothing to disclose. Conflict of interest: H. Hebestreit reports grants and personal fees from Vertex Pharmaceuticals, grants from Mukoviszidose e.V. (German CF Organization), outside the submitted work; and is the Coordinator of the European Cystic Fibrosis Society Exercise Working Group who discuss exercise testing and organise respective symposia., (Copyright ©ERS 2019.)

The vicious circle of dyspnoea-inactivity has been proposed, but never validated empirically, to explain the clinical course of chronic obstructive pulmonary disease (COPD). We aimed to develop and validate externally a comprehensive vicious circle model.We utilised two methods. 1) Identification and validation of all published vicious circle models by a systematic literature search and fitting structural equation models to longitudinal data from the Spanish PAC-COPD (Phenotype and Course of COPD) cohort (n=210, mean age 68 years, mean forced expiratory volume in 1 s (FEV 1 ) 54% predicted), testing both the hypothesised relationships between variables in the model ("paths") and model fit. 2) Development of a new model and external validation using longitudinal data from the Swiss and Dutch ICE COLD ERIC (International Collaborative Effort on Chronic Obstructive Lung Disease: Exacerbation Risk Index Cohorts) cohort (n=226, mean age 66 years, mean FEV 1 57% predicted).We identified nine vicious circle models for which structural equation models confirmed most hypothesised paths but showed inappropriate fit. In the new model, airflow limitation, hyperinflation, dyspnoea, physical activity, exercise capacity and COPD exacerbations remained related to other variables and model fit was appropriate. Fitting it to ICE COLD ERIC, all paths were replicated and model fit was appropriate.Previously published vicious circle models do not fully explain the vicious circle concept. We developed and externally validated a new comprehensive model that gives a more relevant role to exercise capacity and COPD exacerbations., Competing Interests: Conflict of interest: A. Agustí reports receiving grants and personal fees from AstraZeneca, GSK and Menarini, grants from MSD, and personal fees from Novartis, Teva and Chiesi, outside the submitted work. Conflict of interest: R. Rodriguez-Roisin reports receiving grants from Almirall and Menarini, personal fees for service on an advisory board from Boehringer Ingelheim, Pearl Therapeutics and Teva, and lecture fees from Novartis and Takeda, during the conduct of the study, all related to COPD. Conflict of interest: J. Garcia-Aymerich reports payments to her institution for consulting and lecturing from AstraZeneca, and receiving lecture fees from Esteve and Chiesi, outside the submitted work., (Copyright ©ERS 2018.)

The pivotal objective of chronic obstructive pulmonary disease (COPD) self-management programmes is behaviour change to avoid moderate and severe exacerbations and improve health related quality of life.In a prospectively planned, controlled study, COPD patients who participated in the "Living well with COPD" (LWWCOPD) self-management intervention were compared with usual care patients from the primary care COPD Cohort ICE COLD ERIC, who did not receive self-management intervention (NCT00706602) The primary outcome was behaviour change and disease-specific health related quality of life after 1 year. Secondary end-points included exacerbation rates. We calculated mixed linear, zero-inflated negative binomial and logistic regression models and used propensity scores to counteract confounding.467 patients, 71 from the LWWCOPD and 396 from the usual care cohort, were included. The differences between intervention and control were 0.54 (95% CI 0.13-0.94) on the Chronic Respiratory Questionnaire domain "mastery", 0.55 (95% CI 0.11-0.99) on "fatigue", 0.54 (0.14-0.93) on "emotional function" and 0.64 (95% CI 0.14-1.14) on "dyspnoea". The intervention considerably reduced the risk of moderate and severe exacerbations (incidence rate ratio 0.36, 95% CI 0.25-0.52).Self-management coaching in primary care improves health-related quality of life and lowers exacerbation rates and health care use., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2018.)

This study aimed to identify simple rules for allocating chronic obstructive pulmonary disease (COPD) patients to clinical phenotypes identified by cluster analyses.Data from 2409 COPD patients of French/Belgian COPD cohorts were analysed using cluster analysis resulting in the identification of subgroups, for which clinical relevance was determined by comparing 3-year all-cause mortality. Classification and regression trees (CARTs) were used to develop an algorithm for allocating patients to these subgroups. This algorithm was tested in 3651 patients from the COPD Cohorts Collaborative International Assessment (3CIA) initiative.Cluster analysis identified five subgroups of COPD patients with different clinical characteristics (especially regarding severity of respiratory disease and the presence of cardiovascular comorbidities and diabetes). The CART-based algorithm indicated that the variables relevant for patient grouping differed markedly between patients with isolated respiratory disease (FEV 1 , dyspnoea grade) and those with multi-morbidity (dyspnoea grade, age, FEV 1 and body mass index). Application of this algorithm to the 3CIA cohorts confirmed that it identified subgroups of patients with different clinical characteristics, mortality rates (median, from 4% to 27%) and age at death (median, from 68 to 76 years).A simple algorithm, integrating respiratory characteristics and comorbidities, allowed the identification of clinically relevant COPD phenotypes., Competing Interests: Conflict of interest: Disclosures can be found alongside this article at erj.ersjournals.com, (Copyright ©ERS 2017.)

Our aim was to comprehensively validate the 1-min sit-to-stand (STS) test in chronic obstructive pulmonary disease (COPD) patients and explore the physiological response to the test.We used data from two longitudinal studies of COPD patients who completed inpatient pulmonary rehabilitation programmes. We collected 1-min STS test, 6-min walk test (6MWT), health-related quality of life, dyspnoea and exercise cardiorespiratory data at admission and discharge. We assessed the learning effect, test-retest reliability, construct validity, responsiveness and minimal important difference of the 1-min STS test.In both studies (n=52 and n=203) the 1-min STS test was strongly correlated with the 6MWT at admission (r=0.59 and 0.64, respectively) and discharge (r=0.67 and 0.68, respectively). Intraclass correlation coefficients (95% CI) between 1-min STS tests were 0.93 (0.83-0.97) for learning effect and 0.99 (0.97-1.00) for reliability. Standardised response means (95% CI) were 0.87 (0.58-1.16) and 0.91 (0.78-1.07). The estimated minimal important difference was three repetitions. End-exercise oxygen consumption, carbon dioxide output, ventilation, breathing frequency and heart rate were similar in the 1-min STS test and 6MWT.The 1-min STS test is a reliable, valid and responsive test for measuring functional exercise capacity in COPD patients and elicited a physiological response comparable to that of the 6MWT., (Copyright ©ERS 2017.)

Personalised medicine aims to tailor medical decisions to the individual patient. A possible approach is to stratify patients according to the risk of adverse outcomes such as exacerbations in chronic obstructive pulmonary disease (COPD). Risk-stratified approaches are particularly attractive for drugs like inhaled corticosteroids or phosphodiesterase-4 inhibitors that reduce exacerbations but are associated with harms. However, it is currently not clear which models are best to predict exacerbations in patients with COPD. Therefore, our aim was to identify and critically appraise studies on models that predict exacerbations in COPD patients. Out of 1382 studies, 25 studies with 27 prediction models were included. The prediction models showed great heterogeneity in terms of number and type of predictors, time horizon, statistical methods and measures of prediction model performance. Only two out of 25 studies validated the developed model, and only one out of 27 models provided estimates of individual exacerbation risk, only three out of 27 prediction models used high-quality statistical approaches for model development and evaluation. Overall, none of the existing models fulfilled the requirements for risk-stratified treatment to personalise COPD care. A more harmonised approach to develop and validate high- quality prediction models is needed to move personalised COPD medicine forward., (Copyright ©ERS 2017.)

Hospitalisations for severe exacerbations of chronic obstructive pulmonary disease are associated with significant physical and psychological consequences including an increase in symptom severity, severe reductions in physical activity, a deleterious effect on skeletal muscle, impaired exercise tolerance/ability to self-care, decline in quality of life, and increased anxiety and depression. As these consequences are potentially amenable to exercise training, there is a clear rationale for pulmonary rehabilitation in the peri/post-exacerbation setting. Although a 2011 Cochrane review was overwhelmingly positive, subsequent trials have shown less benefit and real-life observational studies have revealed poor acceptability. Qualitative studies have demonstrated that the patient experience is a determining factor while the presence of comorbidities may influence referral, adherence and response to pulmonary rehabilitation. Systematic reviews of less supervised interventions, such as self-management, have shown limited benefits in the post-exacerbation setting. The recent update of the Cochrane review of peri-exacerbation pulmonary rehabilitation showed that benefits were associated with the "comprehensive" nature of the intervention (the number of sessions received, the intensity of exercise training and education delivered, and the degree of supervision) but implementation is demanding. The challenge is to develop interventions that are deliverable and acceptable around the time of an acute exacerbation but also deliver the desired clinical impact., Competing Interests: can be found alongside this article at openres.ersjournals.com

No current patient-centred instrument captures all dimensions of physical activity in chronic obstructive pulmonary disease (COPD). Our objective was item reduction and initial validation of two instruments to measure physical activity in COPD.Physical activity was assessed in a 6-week, randomised, two-way cross-over, multicentre study using PROactive draft questionnaires (daily and clinical visit versions) and two activity monitors. Item reduction followed an iterative process including classical and Rasch model analyses, and input from patients and clinical experts.236 COPD patients from five European centres were included. Results indicated the concept of physical activity in COPD had two domains, labelled "amount" and "difficulty". After item reduction, the daily PROactive instrument comprised nine items and the clinical visit contained 14. Both demonstrated good model fit (person separation index >0.7). Confirmatory factor analysis supported the bidimensional structure. Both instruments had good internal consistency (Cronbach's α>0.8), test-retest reliability (intraclass correlation coefficient ≥0.9) and exhibited moderate-to-high correlations (r>0.6) with related constructs and very low correlations (r<0.3) with unrelated constructs, providing evidence for construct validity.Daily and clinical visit "PROactive physical activity in COPD" instruments are hybrid tools combining a short patient-reported outcome questionnaire and two activity monitor variables which provide simple, valid and reliable measures of physical activity in COPD patients., (Copyright ©ERS 2015.)

Field walking tests are commonly employed to evaluate exercise capacity, assess prognosis and evaluate treatment response in chronic respiratory diseases. In recent years, there has been a wealth of new literature pertinent to the conduct of the 6-min walk test (6MWT), and a growing evidence base describing the incremental and endurance shuttle walk tests (ISWT and ESWT, respectively). The aim of this document is to describe the standard operating procedures for the 6MWT, ISWT and ESWT, which can be consistently employed by clinicians and researchers. The Technical Standard was developed by a multidisciplinary and international group of clinicians and researchers with expertise in the application of field walking tests. The procedures are underpinned by a concurrent systematic review of literature relevant to measurement properties and test conduct in adults with chronic respiratory disease. Current data confirm that the 6MWT, ISWT and ESWT are valid, reliable and responsive to change with some interventions. However, results are sensitive to small changes in methodology. It is important that two tests are conducted for the 6MWT and ISWT. This Technical Standard for field walking tests reflects current evidence regarding procedures that should be used to achieve robust results., (©ERS 2014.)

This European Respiratory Society (ERS) statement provides a comprehensive overview on physical activity in patients with chronic obstructive pulmonary disease (COPD). A multidisciplinary Task Force of experts representing the ERS Scientific Group 01.02 "Rehabilitation and Chronic Care" determined the overall scope of this statement through consensus. Focused literature reviews were conducted in key topic areas and the final content of this Statement was agreed upon by all members. The current knowledge regarding physical activity in COPD is presented, including the definition of physical activity, the consequences of physical inactivity on lung function decline and COPD incidence, physical activity assessment, prevalence of physical inactivity in COPD, clinical correlates of physical activity, effects of physical inactivity on hospitalisations and mortality, and treatment strategies to improve physical activity in patients with COPD. This Task Force identified multiple major areas of research that need to be addressed further in the coming years. These include, but are not limited to, the disease-modifying potential of increased physical activity, and to further understand how improvements in exercise capacity, dyspnoea and self-efficacy following interventions may translate into increased physical activity. The Task Force recommends that this ERS statement should be reviewed periodically (e.g. every 5-8 years)., (©ERS 2014.)

Although physical activity is considered an important therapeutic target in chronic obstructive pulmonary disease (COPD), what "physical activity" means to COPD patients and how their perspective is best measured is poorly understood. We designed a conceptual framework, guiding the development and content validation of two patient reported outcome (PRO) instruments on physical activity (PROactive PRO instruments). 116 patients from four European countries with diverse demographics and COPD phenotypes participated in three consecutive qualitative studies (63% male, age mean±sd 66±9 years, 35% Global Initiative for Chronic Obstructive Lung Disease stage III-IV). 23 interviews and eight focus groups (n = 54) identified the main themes and candidate items of the framework. 39 cognitive debriefings allowed the clarity of the items and instructions to be optimised. Three themes emerged, i.e. impact of COPD on amount of physical activity, symptoms experienced during physical activity, and adaptations made to facilitate physical activity. The themes were similar irrespective of country, demographic or disease characteristics. Iterative rounds of appraisal and refinement of candidate items resulted in 30 items with a daily recall period and 34 items with a 7-day recall period. For the first time, our approach provides comprehensive insight on physical activity from the COPD patients' perspective. The PROactive PRO instruments' content validity represents the pivotal basis for empirically based item reduction and validation., (©ERS 2014.)

Chronic obstructive pulmonary disease (COPD) is associated with increased cardiovascular mortality. Endothelial dysfunction may underpin this association. This cross-sectional study aimed to determine the impact of airflow obstruction, systemic inflammation, oxidative stress, sympathetic activation, hypoxaemia and physical activity on endothelial function in COPD. In stable COPD patients, assessments of endothelial function by flow-mediated dilatation (FMD), cardiovascular risk (Pocock score), airflow obstruction (forced expiratory volume in 1 s (FEV1)), systemic inflammation (high-sensitivity C-reactive protein and interleukin-6), oxidative stress (malondialdehyde), sympathetic activation (baroreflex sensitivity), hypoxaemia (arterial oxygen tension), hypercapnia (arterial carbon dioxide tension (PaCO2)), physical activity (steps per day) and exercise capacity (6-min walking distance) were performed. Associations between FMD and potential determinants were assessed in univariate and multivariate analyses. 106 patients (Global Initiative for Chronic Obstructive Lung Disease stage I/II 35%, stage III 25% and stage IV 40%) were included. In multivariate analysis FEV1 was positively associated with FMD, independent of other significant FMD determinants from univariate analysis (sex, smoking, combined inhaled long-acting β-adrenergic and steroid medication, heart rate, baroreflex sensitivity and PaCO2) and adjusted for potential confounders (cardiovascular risk and age). In addition, the FMD and FEV1 association was modified by physical activity. The findings of this study demonstrate that the severity of airflow obstruction is a significant determinant of endothelial function in patients with COPD. A high level of physical activity seems to have a favourable effect on this association.

Exercise tests are important to characterise chronic obstructive pulmonary disease patients and predict their prognosis, but are often not available outside of rehabilitation or research settings. Our aim was to assess the predictive performance of the sit-to-stand and handgrip strength tests. The prospective cohort study in Dutch and Swiss primary care settings included a broad spectrum of patients (n=409) with Global Initiative for Chronic Obstructive Lung Disease stages II to IV. To assess the association of the tests with outcomes, we used Cox proportional hazards (mortality), negative binomial (centrally adjudicated exacerbations) and mixed linear regression models (longitudinal health-related quality of life) while adjusting for age, sex and severity of disease. The sit-to-stand test was strongly (adjusted hazard ratio per five more repetitions of 0.58, 95% CI 0.40-0.85; p=0.004) and the handgrip strength test moderately strongly (0.84, 95% CI 0.72-1.00; p=0.04) associated with mortality. Both tests were also significantly associated with health-related quality of life but not with exacerbations. The sit-to-stand test alone was a stronger predictor of 2-year mortality (area under curve 0.78) than body mass index (0.52), forced expiratory volume in 1 s (0.61), dyspnoea (0.63) and handgrip strength (0.62). The sit-to-stand test may close an important gap in the evaluation of exercise capacity and prognosis of chronic obstructive pulmonary disease patients across practice settings.